2,5-Dibromopyridine → N-(3-(5-bromopyridin-2-yl)oxetan-3-yl)-2-methylpropane-2-sulfinamide

HRID 525586Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.C([Li])CCC.[CH3:14][C:15]([S:18]([N:20]=[C:21]1[CH2:24][O:23][CH2:22]1)=[O:19])([CH3:17])[CH3:16]>C1(C)C=CC=CC=1>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([C:21]2([NH:20][S:18]([C:15]([CH3:17])([CH3:16])[CH3:14])=[O:19])[CH2:24][O:23][CH2:22]2)=[N:3][CH:4]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a toluene (20 ml) solution of 2,5-dibromopyridine (1.93 g, 8.16 mmol) that is cooled to −78° C. in an atmosphere of nitrogen is added n-butyllithium (2.5 M in hexanes, 3.6 ml, 8.98 mmol) dropwise via syringe over a period of five minutes. The reaction mixture is stirred at −78° C. for ten minutes more before 2-methyl-N-(oxetan-3-ylidene)propane-2-sulfinamide (1.43 g, 8.16 mmol) is added all at once as a concentrated solution in toluene. The reaction is stirred for 30 minutes at −78° C. and for 20 minutes at 0° C. before it is quenched with saturated aqueous ammonium chloride (5 ml). The volatiles were removed by rotary evaporation at reduced pressure. The residual material is partitioned between water (20 ml) and methylene chloride (50 ml). The aqueous is extracted once more with methylene chloride (30 ml). The combined extracts were concentrated and the residual material is subjected to flash column chromatography using a gradient of acetone in hexanes (20% to 75% over 5 column volumes) to provide N-(3-(5-bromopyridin-2-yl)oxetan-3-yl)-2-methylpropane-2-sulfinamide (850 mg): 1H NMR (400 MHz, CDCl3) 1.32 (s, 9 H) 4.91-4.97 (m, 2 H) 5.13 (d, 1 H) 5.34 (d, 1 H) 7.78 (d, 1 H) 8.04 (m, 1 H) 8.68 (d, 1 H); m/z (Cl) 333, 335 [m+H]+.

Workup

customis quenched with saturated aqueous ammonium chloride (5 ml)
customThe volatiles were removed by rotary evaporation at reduced pressure
customThe residual material is partitioned between water (20 ml) and methylene chloride (50 ml)
extractionThe aqueous is extracted once more with methylene chloride (30 ml)
concentrationThe combined extracts were concentrated

Sources & evidence

ORD record: ord-4f0a4eb02df4424dab293ced2fd0538f
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09340564B2

Reaction notes

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